Chrysin promotes the survival of flaps through the TLR4/NF-κB/NLRP3 signaling pathway.

Abstract

Flap necrosis is a common postoperative complication primarily caused by ischemia-reperfusion injury and impaired angiogenesis. This study investigated the therapeutic effects and mechanisms of chrysin, a natural flavonoid compound extracted from medicinal plants including Oroxylum indicum, Scutellaria baicalensis, and Passiflora spp, on the survival of random skin flaps. We employed network pharmacology to analyze chrysin's mechanism of action, predicting its therapeutic targets in ischemic diseases through cross-analysis of its potential targets with the pathophysiological mechanisms of ischemia-reperfusion injury. Molecular docking technology was used to simulate the optimal binding conformation and affinity between chrysin and its target receptors. Additionally, a modified McFarlane flap model was established in 36 Sprague-Dawley rats randomly divided into control, low-dose (10 mg/kg/day), and high-dose (40 mg/kg/day) groups (n = 12 each). Flap survival was evaluated 7 days postoperatively, along with assessments of TLR4/NF-κB/NLRP3 signaling pathway expression, tissue inflammation, oxidative stress levels, and blood perfusion. Chrysin treatment significantly improved flap survival rate in a dose-dependent manner. The mechanisms involved were 1) inhibiting activation of the TLR4/NF-κB/NLRP3 inflammatory signaling pathway; 2) reducing oxidative stress damage; and 3) promoting angiogenesis through upregulation of VEGF-A expression. This study demonstrates that the plant-derived flavonoid chrysin improves flap survival through multiple mechanisms, including anti-inflammatory, antioxidant, and pro-angiogenic effects, providing a potential phytotherapeutic strategy for preventing and treating flap necrosis. These findings not only elucidate the pharmacological mechanisms of chrysin but also provide theoretical foundations for developing natural product-based adjuvant therapies in surgery.